Genetic and endocrine factors are implicated in the etiology of attention deficit disorder with hyperactivity[unreadable] (ADHD). Polychlorinated biphenyls (PCBs) and, we suggest, polybrominated diphenyl ethers (PBDEs)[unreadable] induce similar deficits in attention and impulse control in developmentally exposed children, as well as[unreadable] reducing central catecholamine and thyroid hormone levels in experimental animals?physiological changes[unreadable] also seen in ADHD. We hypothesize that developmental exposure to PCBs and PBDEs, due to their ability[unreadable] to alter central catecholamines and/or thyroid hormones during critical periods of development, are etiologic[unreadable] factors responsible for the contaminant induced behavioral changes that are reminiscent of those seen in[unreadable] ADHD. To better understand the physiological bases for these behavioral alterations and to gain insights to[unreadable] the etiology of ADHD we will determine: (i) the effects of these contaminants, alone and in combination, on[unreadable] central catecholamines and maternal and offspring circulating thyroid hormone levels; (ii) whether[unreadable] experimental reductions in maternal and fetal circulating thyroid hormones (induced with methimazole) mimic[unreadable] the changes seen in central catecholamines with PCBs and/or PBDEs; (iii) whether contaminant-induced[unreadable] reductions in central catecholamines can be ameliorated following either maternal T4 supplementation or[unreadable] adult methylphenidate exposure and (iv) the effects of these manipulations on mRNA expression and[unreadable] proteins that regulate catecholamine function in prefrontal cortex, striatum and hippocampus. These studies,[unreadable] when combined with behavioral data from similarly exposed animals, will begin to determine the[unreadable] mechanisms by which these contaminants alter behaviors reminiscent of ADHD in developmentally exposed[unreadable] children, including the relative contributions that contaminant induced reductions in central catecholamines[unreadable] and thyroid hormone levels play in altering nervous system development and ultimately behavior.[unreadable]